Biology:Mothers against decapentaplegic homolog 6

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

SMAD family member 6, also known as SMAD6, is a protein that in humans is encoded by the SMAD6 gene.

SMAD6 is a protein that, as its name describes, is a homolog of the Drosophila gene "mothers against decapentaplegic". It belongs to the SMAD family of proteins, which belong to the TGFβ superfamily of modulators. Like many other TGFβ family members SMAD6 is involved in cell signalling. It acts as a regulator of TGFβ family (such as bone morphogenetic proteins) activity by competing with SMAD4 and preventing the transcription of SMAD4's gene products. There are two known isoforms of this protein.

Nomenclature

The SMAD proteins are homologs of both the drosophila protein, mothers against decapentaplegic (MAD) and the C. elegans protein SMA. The name is a combination of the two. During Drosophila research, it was found that a mutation in the gene MAD in the mother repressed the gene decapentaplegic in the embryo. The phrase "Mothers against" was added as a humorous take-off on organizations opposing various issues e.g., Mothers Against Drunk Driving, or MADD; and based on a tradition of such unusual naming within the gene research community.

Disease associations

Heterozygous, damaging mutations in SMAD6 are the most frequent genetic cause of non-syndromic craniosynostosis identified to date.

Interactions

Mothers against decapentaplegic homolog 6 has been shown to interact with:

• HOXC8,
• MAP3K7,
• Mothers against decapentaplegic homolog 7,
• PIAS4, and
• STRAP.

Further reading

• "TGF-beta signal transduction". Annu. Rev. Biochem. 67: 753–91. 1998. doi:10.1146/annurev.biochem.67.1.753. PMID 9759503. 
• "Remarkable versatility of Smad proteins in the nucleus of transforming growth factor-beta activated cells". Cytokine Growth Factor Rev. 10 (3–4): 187–99. 2000. doi:10.1016/S1359-6101(99)00012-X. PMID 10647776. 
• "The Smad pathway". Cytokine Growth Factor Rev. 11 (1–2): 5–13. 2000. doi:10.1016/S1359-6101(99)00024-6. PMID 10708948. 
• "TGF-beta signaling by Smad proteins". Cytokine Growth Factor Rev. 11 (1–2): 15–22. 2000. doi:10.1016/S1359-6101(99)00025-8. PMID 10708949. 
• "Mad-related genes in the human". Nat. Genet. 13 (3): 347–9. 1996. doi:10.1038/ng0796-347. PMID 8673135. 
• "Vascular MADs: Two novel MAD-related genes selectively inducible by flow in human vascular endothelium". Proc. Natl. Acad. Sci. U.S.A. 94 (17): 9314–9. 1997. doi:10.1073/pnas.94.17.9314. PMID 9256479. Bibcode: 1997PNAS...94.9314T. 
• "Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor". Genes Dev. 12 (2): 186–97. 1998. doi:10.1101/gad.12.2.186. PMID 9436979. 
• "Induction of inhibitory Smad6 and Smad7 mRNA by TGF-beta family members". Biochem. Biophys. Res. Commun. 249 (2): 505–11. 1998. doi:10.1006/bbrc.1998.9170. PMID 9712726. 
• "A role for smad6 in development and homeostasis of the cardiovascular system". Nat. Genet. 24 (2): 171–4. 2000. doi:10.1038/72835. PMID 10655064. 
• "Smad6 as a transcriptional corepressor". J. Biol. Chem. 275 (12): 8267–70. 2000. doi:10.1074/jbc.275.12.8267. PMID 10722652. 
• "BMP2-induced apoptosis is mediated by activation of the TAK1-p38 kinase pathway that is negatively regulated by Smad6". J. Biol. Chem. 275 (23): 17647–52. 2000. doi:10.1074/jbc.M908622199. PMID 10748100. 
• "STRAP and Smad7 Synergize in the Inhibition of Transforming Growth Factor β Signaling". Mol. Cell. Biol. 20 (9): 3157–67. 2000. doi:10.1128/MCB.20.9.3157-3167.2000. PMID 10757800. 
• "Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation". J. Biol. Chem. 276 (16): 12477–80. 2001. doi:10.1074/jbc.C100008200. PMID 11278251. 
• "Promoting bone morphogenetic protein signaling through negative regulation of inhibitory Smads". EMBO J. 20 (15): 4132–42. 2001. doi:10.1093/emboj/20.15.4132. PMID 11483516. 
• "Inhibition of BMP2-induced, TAK1 kinase-mediated neurite outgrowth by Smad6 and Smad7". Genes Cells 6 (12): 1091–9. 2002. doi:10.1046/j.1365-2443.2001.00483.x. PMID 11737269. 
• "Inhibitory smads and tgf-Beta signaling in glomerular cells". J. Am. Soc. Nephrol. 13 (11): 2657–66. 2003. doi:10.1097/01.ASN.0000033276.06451.50. PMID 12397035.